Lymphocytes from one individual stimulate those of another into mitosis when the cells are incubated together. This mixed lymphocyte response (MLR) may result in generation of cytotoxic T-cells, and is controlled by genes in the major histocompatibility complex (MHC). HLA-A, B, and C gene products are the apparent primary targets for cytotoxic T-cells, while the mitotic response is induced by HLA-D products, which may be the serologically detectable HLA-DR antigens. Specific autologous-restricted cytotoxic T-cells and a mitotic response can also be generated in lymphocytes by autologous lymphocytes infected with measles virus. We propose to study the specificity of the cytotoxic and proliferating lymphocytes in these responses at a molecular level using a series of mutant B-cell lines, from individuals available as responders, lacking particular HLA-A, B, C and DR antigens. We will compare them to each other and the parent cell line for susceptibility to lysis by allogeneic cytotoxic T-cells, and, after infection, by measles virus-specific autologous cytotoxic T-cells. They will be compared for their ability to induce the MLR, a proliferative autologous response when infected with measles virus, and to provoke secondary proliferative responses following primary stimulation with allogeneic lymphocytes, or, when infected, following primary stimulation with infected lymphocytes. We will examine the binding specificity of stimulated lymphocytes using 125I or fluorescein-labeled aggregates of membrane glycoproteins isolated from B-cell lines, and examine the role of protease. We will quantitate antigen-binding cells in the MLR by autoradiography and immunofluorescence, and determine their specificity for HLA-A, B, C and DR molecules. We will examine antigen-binding cells in the virus response, using aggregates from B-cell lines persistently infected with measles virus, with respect to the role of HLA antigens in the formation of target determinants. We will study the role of T and B-lymphocytes and monocytes in the autologous measles virus response. We will also investigate the molecular basis of the interaction between the proliferating and precytotoxic population which enhances the cytotoxic response.